Statin Drugs Are Associated With Response to Immune Checkpoint Blockade in Recurrent/Metastatic Head and Neck Cancer

ABSTRACT Background Statin drugs, frequently used to treat hyperlipidemia, are associated with improved survival outcomes in multiple solid tumor types, including head and neck squamous cell carcinoma (HNSCC). Preclinical studies suggest that manipulation of cholesterol with statins and other agents...

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Main Authors: Tyler J. Kristoff, Sean Evans, Pranay Nayi, Marin Abousaud, Subir Goyal, Yuan Liu, Dong Shin, Conor E. Steuer, Nabil F. Saba, Nicole C. Schmitt
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70718
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author Tyler J. Kristoff
Sean Evans
Pranay Nayi
Marin Abousaud
Subir Goyal
Yuan Liu
Dong Shin
Conor E. Steuer
Nabil F. Saba
Nicole C. Schmitt
author_facet Tyler J. Kristoff
Sean Evans
Pranay Nayi
Marin Abousaud
Subir Goyal
Yuan Liu
Dong Shin
Conor E. Steuer
Nabil F. Saba
Nicole C. Schmitt
author_sort Tyler J. Kristoff
collection DOAJ
description ABSTRACT Background Statin drugs, frequently used to treat hyperlipidemia, are associated with improved survival outcomes in multiple solid tumor types, including head and neck squamous cell carcinoma (HNSCC). Preclinical studies suggest that manipulation of cholesterol with statins and other agents can enhance the function of multiple components involved in anti‐tumor immune responses. Retrospective studies in other solid tumor types suggest that statin therapy is associated with improved responses to immune checkpoint blockade (ICB), but this has not yet been investigated in HNSCC. Methods Pharmacy records were searched for patients with recurrent/metastatic HNSCC treated at our institution with pembrolizumab or nivolumab from 2015 to 2022. Patients who received less than 3 doses of ICB were excluded. Univariate and multivariate analyses were performed to determine the association between statin use and objective response, progression‐free survival (PFS) and overall survival (OS). Results A total of 158 patients were included. Statins were significantly associated with objective response; the strongest associations were seen with rosuvastatin and lovastatin. On multivariate analyses, statins were independently associated with objective response but not with PFS or OS. Conclusions Statin therapy appears to be an independent predictor of response to ICB in HNSCC. Larger, prospective studies are needed to determine whether specific statin drugs can improve survival outcomes in ICB‐treated patients.
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spelling doaj-art-abe98a7b60bc4c9b9f46784acd1e402c2025-08-20T02:05:21ZengWileyCancer Medicine2045-76342025-03-01145n/an/a10.1002/cam4.70718Statin Drugs Are Associated With Response to Immune Checkpoint Blockade in Recurrent/Metastatic Head and Neck CancerTyler J. Kristoff0Sean Evans1Pranay Nayi2Marin Abousaud3Subir Goyal4Yuan Liu5Dong Shin6Conor E. Steuer7Nabil F. Saba8Nicole C. Schmitt9Department of Hematology and Medical Oncology Emory University Atlanta Georgia USADepartment of Hematology and Medical Oncology Emory University Atlanta Georgia USAChildren's Healthcare of Atlanta Atlanta Georgia USAAstellas Pharma Global Development Inc Northbrook Illinois USADepartment of Biostatistics and Bioinformatics Rollins School of Public Health of Emory University Atlanta Georgia USADepartment of Biostatistics and Bioinformatics Rollins School of Public Health of Emory University Atlanta Georgia USADepartment of Hematology and Medical Oncology Emory University Atlanta Georgia USADepartment of Hematology and Medical Oncology Emory University Atlanta Georgia USADepartment of Hematology and Medical Oncology Emory University Atlanta Georgia USAWinship Cancer Institute, Emory University Atlanta Georgia USAABSTRACT Background Statin drugs, frequently used to treat hyperlipidemia, are associated with improved survival outcomes in multiple solid tumor types, including head and neck squamous cell carcinoma (HNSCC). Preclinical studies suggest that manipulation of cholesterol with statins and other agents can enhance the function of multiple components involved in anti‐tumor immune responses. Retrospective studies in other solid tumor types suggest that statin therapy is associated with improved responses to immune checkpoint blockade (ICB), but this has not yet been investigated in HNSCC. Methods Pharmacy records were searched for patients with recurrent/metastatic HNSCC treated at our institution with pembrolizumab or nivolumab from 2015 to 2022. Patients who received less than 3 doses of ICB were excluded. Univariate and multivariate analyses were performed to determine the association between statin use and objective response, progression‐free survival (PFS) and overall survival (OS). Results A total of 158 patients were included. Statins were significantly associated with objective response; the strongest associations were seen with rosuvastatin and lovastatin. On multivariate analyses, statins were independently associated with objective response but not with PFS or OS. Conclusions Statin therapy appears to be an independent predictor of response to ICB in HNSCC. Larger, prospective studies are needed to determine whether specific statin drugs can improve survival outcomes in ICB‐treated patients.https://doi.org/10.1002/cam4.70718head and neck cancerimmune checkpoint blockadeimmunotherapyPD‐1PD‐L1squamous cell carcinoma
spellingShingle Tyler J. Kristoff
Sean Evans
Pranay Nayi
Marin Abousaud
Subir Goyal
Yuan Liu
Dong Shin
Conor E. Steuer
Nabil F. Saba
Nicole C. Schmitt
Statin Drugs Are Associated With Response to Immune Checkpoint Blockade in Recurrent/Metastatic Head and Neck Cancer
Cancer Medicine
head and neck cancer
immune checkpoint blockade
immunotherapy
PD‐1
PD‐L1
squamous cell carcinoma
title Statin Drugs Are Associated With Response to Immune Checkpoint Blockade in Recurrent/Metastatic Head and Neck Cancer
title_full Statin Drugs Are Associated With Response to Immune Checkpoint Blockade in Recurrent/Metastatic Head and Neck Cancer
title_fullStr Statin Drugs Are Associated With Response to Immune Checkpoint Blockade in Recurrent/Metastatic Head and Neck Cancer
title_full_unstemmed Statin Drugs Are Associated With Response to Immune Checkpoint Blockade in Recurrent/Metastatic Head and Neck Cancer
title_short Statin Drugs Are Associated With Response to Immune Checkpoint Blockade in Recurrent/Metastatic Head and Neck Cancer
title_sort statin drugs are associated with response to immune checkpoint blockade in recurrent metastatic head and neck cancer
topic head and neck cancer
immune checkpoint blockade
immunotherapy
PD‐1
PD‐L1
squamous cell carcinoma
url https://doi.org/10.1002/cam4.70718
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